Since most of newly developed drugs are poorly soluble, it is required to improve the solubility or absorption.
A method of increasing solubility of the existing poorly soluble drugs includes chemical modification and physical modification. The chemical modification includes salt addition, aqueous prodrug approach, and the like, and the physical modification includes modification of particle size or crystal form, formation of crystalline polymorph, formation of complex using a surfactant or cyclodextrin, drug dispersion using a dispersant, and the like. To increase solubility or absorption of drugs, drug formulation methods such as micronization, noncrystallization, solid dispersion formation, and the like have been suggested, among which solid dispersion formation has been widely examined as a means for dispersing a drug in an inactive carrier.
As the solid dispersion preparation method, several methods have been suggested, and particularly, a solvent method is a practical method. According to the solvent method, a drug and an aqueous polymer carrier are dissolved in a solvent such as an organic solvent, and the like, and the solvent is removed by distillation, or a drug is dissolved in a solvent and dispersed in a carrier, and then, the solvent is removed by distillation to prepare a solid dispersion.
As the solvent method, it is reported in Japanese Patent Publication No. 3-1288 and Japanese Patent No. 3028404 that a poorly soluble drug, nifedipine and a polymer substrate such as polyvinylpyrrolidone, hydroxymethylcellulose, methylcellulose, and the like are dissolved in an organic solvent, and the solution is spray dried to obtain a solid dispersion in a microgranule form wherein lactose, and the like is assembled with an aqueous polymer such as hydroxypropylcellulose.
A poorly soluble drug, fenofibrate has very low water solubility. Fenofibrate, (2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoic acid, 1-methylethyl ester) is one of fibrate drugs. There have been a lot of efforts to improve a fenofibrate formulation, particularly bioavailability of fennofibrate. U.S. Pat. Nos. 4,895,726 and 5,880,148 disclose that fenofibrate is co-micronized with a surfactant.
Several patents disclose specific formulations of micronized fenofibrate and a specific polymer additive or surfactant additive, while other patents disclose fenofibrate emulsion and suspension.
US Patent No. 20030224059 discloses a micronized particle formed of an active pharmaceutical ingredient having low water solubility and a solid solution of a sublimable carrier, a drug delivery vehicle comprising the same, and a preparation method thereof.
Micronization of fenofibrate or combination of a surfactant and micronized fenofibrate may increase bioavailability of fenofibrate to some degree, thus decreasing administration amount thereof while maintaining the bioavailability at eating. However, since practical bioavailability of fenofibrate is still low and the use of a surfactant may induce toxicity to human body, there is still a demand for the improvement.